Airway smooth muscle in vivo is exposed to hormones and humors, e.g. catecholamines, cholinergic stimuli, prostaglandins and steroids. Interactions between them may modulate the response of airway smooth muscle to contractile and relaxant agonists. Our objective is to examine the interactions between prostaglandins and catecholamines, particularly in respect to beta-adrenoceptor regulation. Methods will include an in vivo determination of airway sensitivity such that a population of guinea pigs is divided into groups which are hyper-, normal and hyporeactive to histamine aerosols. We will determine airway sensitivities in the subgroups in vivo to histamine and bronchodilator drugs, e.g. catecholamines, before and after the induction of beta-adrenoceptor or prostaglandin receptor tachyphylaxis. Tachyphylaxis will be induced by chronic exposure to a variety of agents. We will determine the duration and reversibility (indomethacin, hydrocortisone) of tachyphylaxis. Adenylate cyclase (from the subgroups and chronically treated animals) will be examined for basal activity and response to isoproterenol, PGE2, protaglandin endoperoxides and sodium flouride. The catecholamine binding capacities of these membrane fractions will be determined using 3(H) alprenolol. In vitro production of prostaglandins by lung, tracheal and bronchial tissues will be determined using bioassay, radioimmunoassay or colorimetric analysis. We will perform similar in vivo and in vitro experiments in which prostaglandin production has been supressed (chronic indomethacin). Our results, we believe, will demonstrate that prostaglandins modify responses mediated by beta-adrenoceptors. Our data will link the biochemical and physiological events in beta-adrenoceptor deficient, hyperreactive, normal and hyporeactive airway smooth muscle. The results will enable us to extend our models of airway smooth muscle function to determine possible causes for airway hyperreactivity in guinea pigs. This in turn will aid in the elucidation of the pathogenesis of disease states associated with airway hyperreactivity in man, e.g., bronchial asthma.